Agranulocytosis is an acute condition involving a severe and dangerous
leukopeniaparticularly of neutrophils causing a neutropeniain the circulating blood. [ [http://www.emedicine.com/asp/dictionary.asp?keyword=agranulocytosis eMedicine/Stedman Medical Dictionary Lookup! ] ] [http://www.emedicine.com/MED/topic82.htm] The meaning of the term can be worked out from the etymologywith the prefix 'a' denoting a reduction in the number of granulocytes in the blood stream [http://www.yourdictionary.com/agranulocytosis] .
Concentrations of granulocytes (a class that includes
neutrophils, basophilsand eosinophils) can often drop to below 500 cells/mm³ of blood), less than a sixth of the reference value of 3-10 x 103 cells/mm³.Fact|date=January 2008
igns and symptoms
Agranulocytosis may be asymptomatic, but may clinically present with sudden fever, rigors and sore throat.
Infectionof any organ may be rapidly progressive (e.g. pneumonia, urinary tract infection). Septicemia may also progress rapidly.
A large number of drugs have been associated with agranulocytosis, including
antiepileptics, antithyroid drugs ( carbimazoleand methimazole), metamizole, antibiotics ( penicillin, chloramphenicoland co-trimoxazole), cytotoxic drugs, gold, NSAIDs ( indomethacin, naproxen, phenylbutazone), the antidepressant mirtazapine, and some antipsychotics (the atypical antipsychotic clozapine) [Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.] . Clozapine users in the US must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC). Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.Fact|date=February 2007
Neutropenia and agranulocytosis are associated with gum disease.Fact|date=April 2007
The diagnosis is made on a
complete blood count, a routine blood test performed frequently in general practice and especially in hospital setting.
The neutrophil count is below 500 and can reach 0 cells/mm3. Other series are normally spared. The myelogram (
bone marrowsample) shows normocellular blood marrow with promyelocyte's maturation arrest. To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasiaand leukemias. This requires a bone marrow examination.
The terms "agranulocytosis", "
granulocytopenia" and " neutropenia" are often used interchangeably, although agranulocytosis implies a more severe deficiency than granulocytopenia, and neutropenia implies a deficiency of neutrophils only. To be precise, neutropenia is the term used to describe absolute neutrophil counts (ANC) <500 per microlitre, whereas agranulocytosis is reserved for cases with ANC <100 per microlitre. The following terms can be used to specify the type of granulocytereferenced:
eosinophil-- eosinopenia- not commonly used
basophil-- basopenia- very rarely used
In patients who have no symptoms of infection, management consists of close monitoring with serial blood counts, withdrawal of the offending agent (e.g. medication) and general advice on the significance of fever.
Infection in patients with low
white blood cellcounts is usually treated urgently, and usually includes a broad-spectrum penicillin or cephalosporin ( piperacillin-tazobactam, ceftazidimeor ticarcillin clavulanate) or meropenemin combination with gentamycinor amikacin.Fact|date=February 2007
If the patient remains febrile after 4-5 days and no causative organism for the infection has been identified, antibiotics are generally changed to a glycopeptide (e.g.
vancomycin), and subsequently an antifungal agent (e.g. amphotericin B) is added to the regimen.Fact|date=February 2007 In agranulocytosis, the use of recombinant G-CSF ( filgrastim) often results in hematologic recovery.Fact|date=February 2007
Transfusion of granulocytes would have been a solution to the problem. However, granulocytes live only ~10 hours in the circulation (for days in
spleenor other tissue), which gives a very short-lasting effect. In addition, there are many complications of such a procedure.
Complete blood count
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